Rate of perceived exertion (RPE) is a clinically convenient indicator for monitoring exercise intensity in cardiopulmonary rehabilitation. It might not be sensitive enough for clinicians to determine the patients' physiological status because its association with the cardiovascular system and local muscle factors is unknown. This study used the electromyographic sensor to detect the local muscle fatigue and stabilization of patella, and analyzed the relationship between various local muscle and cardiovascular factors and the increase of RPE during stepping exercise, a common exercise program provided in cardiopulmonary rehabilitation. Ten healthy adults (4 males and 6 females) participated in this study. Each subject used their right bare foot to step up onto a 23-cm-high step at a constant speed until the RPE score reached 20. The RPE, heart rate (HR), and surface EMG of the rectus femoris (RF), vastus medialis, and vastus lateralis were recorded at 1-minute intervals during the stepping exercise. The generalized estimating equations (GEE) analysis indicated that the increase in RPE significantly correlated with the increase in HR, and decrease in median frequency (MF) of the EMG power spectrum of the RF. Experimental results suggest that the increase in RPE during stepping exercise was influenced by the cardiovascular status, localized muscle fatigue in the lower extremities. The weighting of the local muscle factors was more than half of the weighting of the cardiovascular factor.